Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)     

工艺参数对陶瓷注射成型的影响与分析

本研究通过改变注射温度，注射压力，保压压力等几个主要参数，对形状，体积不同的注射成型体，试条，圆柱及子部件进行了一系列注射工艺实验。相应地对成型体的密度，弯曲强度及烧结体的密度和强度进行测量，并从陶瓷注射成型混合物的流动行为，热物理特性方面对注射这一复杂过程进行分析，探讨工艺参数对成型过程的内在影响，从而确定合理的注射工艺条件。     

Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate,Fenofibric Acid,and Pemafibrate

Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment.     

Stabilizing effect of the cyclodextrins additive to spray-dried particles of curcumin/polyvinylpyrrolidone on the supersaturated state of curcumin

Although curcumin is considered to have various therapeutic effects, its use as a functional food or supplement is restricted owing to its low water solubility and bioavailability. To increase the solubility of curcumin in water, the use of polyvinylpyrrolidone (PVP) and vinylpyrrolidone-vinyl acetate copolymers with a pyrrolidone skeleton was noted to be promising. In particular, the bi-component formulations of curcumin/PVP prepared through spray drying exhibited an amorphous state in powder X-ray diffraction observations and temporally increased the apparent solubility of curcumin to over 5000 times that of untreated curcumin; nevertheless, after 24 h, the solubility decreased owing to the unstable supersaturated state of curcumin. The addition of α-cyclodextrin (α-CyD) in the bi-component curcumin/PVP formulation helped maintain the supersaturated state of curcumin, whereas the addition of β- and γ-CyD led to the collapse of the supersaturated state. The addition of α-CyD can likely help inhibit the nucleation and crystal growth of curcumin, through the interaction among the solubilized units of curcumin/PVP and α-CyD.     

Influence of Cu metal on the domain structure and carrier mobility in single-layer graphene

We demonstrate that domain structure of single-layer graphene grown by ambient pressure chemical vapor deposition is strongly dependent on the crystallinity of the Cu catalyst. Low energy electron microscopy analysis reveals that graphene grown using a Cu foil gives small and mis-oriented graphene domains with a number of domain boundaries. On the other hand, no apparent domain boundaries are observed in graphene grown over a heteroepitaxial Cu(111) film deposited on sapphire due to unified orientation of graphene hexagons. The difference in the domain structures is correlated with the difference in the crystal plane and grain structure of the Cu metal. The graphene film grown on the heteroepitaxial Cu film exhibits much higher carrier mobility than that grown on the Cu foil.     

Investigation of ring-opening polymerization of 5-[2-{2-(2-methoxyethoxy)ethoxy}-ethoxymethyl]-5-methyl-1,3-dioxa-2-one by organometallic catalysts

To develop new polymer-based materials, the design of aliphatic carbonate has received attention and become a well-known cyclic monomer. In view of carbonate ring polymer scope, poly(trimethylene carbonate) (PTMC) has been continuously developed for further applications due to its unique degradability. PTMC bearing oligo ethylene glycol units, PTMCM-MOE3OM, were typically prepared via ring-opening polymerization (ROP) using amidine-based catalysts such as 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) and benzyl alcohol (BnOH) as an initiator. To improve the polymer molecular weight or other properties, several know-how synthetic catalysts based on organometallic complexes are under consideration as potential catalysts. With the existence of diverse classes of metallic complexes, the inorganic complexes were investigated for their catalytic activity based on tris(dimethylsilyl)amido chelating, bis(phenolate) chelating, and macrocyclic tetradentate (NNNN)-type cyclen chelating with a metal-core of tin (II), scandium (III), lutetium (III), and zinc (II). In this study, we found that involving a Zn(II) dimethylcyclen/alkoxide ligand and Mg complexes could accelerate the reaction and finish the polymerization under ambient conditions within 2 hr. Molecular weight reached 11,000 g/mol (40%) and 8,100 g/mol (> 96%). Subsequently, we concluded that Zn and Mg complexes were high reactivity for initiating the ROP of TMCM-MOE3OM upon steadily degree of polymerization.     

Temperature-responsive culture surfaces for insect cell sheets to fabricate a bioactuator

ABSTRACT

For the first time, we have fabricated insect-derived cell sheets by using temperature-responsive culture surfaces having a phase-transition temperature below 25°C. We prepared the temperature-responsive cell culture surfaces (tissue culture polystyrene, TCPS) by grafting a copolymeric gel consisting of hydrophobic N-tert-butylacrylamide (tBAAm) and N-isopropylacrylamide (IPAAm) units. First, to characterize the hydrophilic and hydrophobic properties of the copolymeric gel-grafted surfaces, static water contact angles of each surface were measured at various temperatures. By increasing the amount of tBAAm in the grafted copolymeric gel, the transition temperature of the gel was shifted to lower temperatures. At 25°C, the grafted copolymeric gel was dehydrated, and the insect-derived cells (AeAl2 cells) adhered on all the copolymeric gel-grafted surfaces. At 20°C, AeAl2 cells cannot adhere on the P(IPAAm-1.62tBAAm)-TCPS surface (the initial molar ratio of IPAAm and tBAAm (tBAAm?=?1.62 mol%)) better than on other surfaces (TCPS and tBAAm?=?4.88, 8.17 mol%). These two findings implied that the lower critical solution temperature of the copolymeric gel-grafted-TCPS existed from 20°C to 25°C. The laminin-coated P(IPAAm-1.62tBAAm)-TCPS surface showed temperature-dependent cell attachment and detachment properties, while AeAl2 cells were not detached from the extracellular matrix uncoated P(IPAAm-1.62tBAAm)-TCPS surface. AeAl2 cells and insect muscle cells were harvested as the respective sheets.     

Rubber‐toughened polyamide‐6 with a low thermal expansion coefficient: effect of preferential distribution of rubber and inorganic filler

The effects of morphological changes on the thermal expansion, toughness and heat resistance of polyamide‐6 (PA)/styrene–ethylene–butylene–styrene (SEBS)/polyphenylene ether (PPE) blends were investigated. Compared with the typical ‘sea (PA matrix)–island (PPE domain)–lake (SEBS in PPE domain)’ morphology, an injection‐molded ternary blend with a preferential distribution of SEBS component at the interface between PA and PPE exhibited a low coefficient of linear thermal expansion (CLTE) in the flow direction. This low CLTE was ascribed to the deformation of SEBS and PA into a co‐continuous microlayer network structure during injection molding. Consequently, the expansion preferentially occurred towards the thickness direction. Further CLTE reduction either by a change in PA viscosity or by the selective location of an inorganic filler was examined, and its influences on impact strength and heat resistance are discussed based on transmission electron microscopy observations. © 2015 Society of Chemical Industry     

Experimental study on method of estimating strength of weld metal in steel structure

We conducted the welding experiment using three kinds of test piece, actual size, diaphragm and butt joint. Then, we examined the influence on strength, cooling time and carbon equivalent of weld metal by welding conditions on the different test pieces. We calculated an estimate of cooling time and chemical components. Consequently, we concluded that the strength of weld metal can be estimated by heat input, interpass temperature, carbon equivarent of welding wire and shape of test piece.